Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation

The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings

Ultrastructure of neurovascular changes in human diabetic retinopathy

The previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures

Age and diabetes related changes of the retinal capillaries: an ultrastructural and immunohistochemical study

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes

Egas Moniz: 90 years (1927-2017) from cerebral angiography

In June 2017 we celebrate the 90th anniversary of the pioneer discovery of cerebral angiography, the seminal imaging technique used for visualizing cerebral blood vessels and vascular alterations as well as other intracranial disorders. Egas Moniz (1874-1955) was the first to describe the use of this revolutionary technique which, until 1975 (when computed tomography, CT, scan was introduced in the clinical practice), was the sole diagnostic tool to provide an imaging of cerebral vessels and therefore alterations due to intracranial pathology. Moniz introduced in the clinical practice this fundamental and important diagnostic tool. The present contribution wishes to pay a tribute to the Portuguese neurosurgeon, who was also a distinguished neurologist and statesman. Despite his tremendous contribution in modern brain imaging, Egas Moniz was awarded the Nobel Prize in Physiology or Medicine in 1949 for prefrontal leucotomy, the neurosurgical intervention nowadays unacceptable, but should rather be remembered for his key contribution to modern brain imaging. KEYWORDS

Trophic and neurotrophic factors in human pituitary adenomas (Review)

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas

Possible involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of the Dupuytren’s contracture: a novel target for a future therapeutic strategy?

Dupuytren’s contracture (DC) is a benign fibroproliferative disease causing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the genesis, progression and recurrence of the disease to optimize therapeutic agents and strategies for controlling Dupuytren’s disease. The expression of pro-inflammatory cytokines and other growth factors was detected by immunohistochemistry and immunofluorescence in the fibrotic nodules and normal palmar fascia resected respectively from patients affected by Dupuytren’s contracture and Carpal Tunnel Syndrome (as negative controls). RT-PCR analysis was performed to quantify the expression of TGF-β1, IL-1β and VEGFa in the myofibroblasts and fibroblasts isolated from Dupuytren’s nodules. Histological analysis showed the high cellularity and rate of proliferation of Dupuytren’s tissue with the presence of myofibroblastic isotypes. Our data showed the strong expression of TGF-β1, IL-1β and VEGFa in Dupuytren’s fibromatosis nodules suggesting a direct role of these markers in the onset, progression and recurrence of the disease. Our observations suggest that TGF-β1, IL-1β and VEGFa may be considered potential therapeutic targets in the treatment of Dupuytren’s disease. Moreover, a new innovative therapy may be represented by the combined use of specific inhibitors of these growth factors

Petroclival clinoidal folds and arachnoidal membranes of the anteromedial incisural space: clinical anatomy for neuro critical care

A systematic and narrative literature review was performed, focusing attention on the anatomy of the area located at the junction of the sphenoid and the basal portion of the temporal bone (petrous bone, petrous apex, upper petro-clival region) encircled by the free edge of the tentorium, the insertion of the tentorium itself to the petrous apex and the anterior and posterior clinoid processes that give rise to three distinct dural folds or ligaments: the anterior petroclinoid ligament, the posterior petroclinoid ligament and the interclinoid ligament. These dural folds constitute the posterior portion of the roof of the cavernous sinus denominated "the oculomotor triangle". The main purpose of this review study was to describe this anatomical region, particularly in the light of the relationships between the anterior margin of the free edge of the tentorium and the above-mentioned components of the sphenoid and petrous bone

Possible involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of the Dupuytren’s contracture: a novel target for a future therapeutic strategy?

Dupuytren’s contracture (DC) is a benign fibroproliferative disease causing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the genesis, progression and recurrence of the disease to optimize therapeutic agents and strategies for controlling Dupuytren’s disease. The expression of pro-inflammatory cytokines and other growth factors was detected by immunohistochemistry and immunofluorescence in the fibrotic nodules and normal palmar fascia resected respectively from patients affected by Dupuytren’s contracture and Carpal Tunnel Syndrome (as negative controls). RT-PCR analysis was performed to quantify the expression of TGF-β1, IL-1β and VEGFa in the myofibroblasts and fibroblasts isolated from Dupuytren’s nodules. Histological analysis showed the high cellularity and rate of proliferation of Dupuytren’s tissue with the presence of myofibroblastic isotypes. Our data showed the strong expression of TGF-β1, IL-1β and VEGFa in Dupuytren’s fibromatosis nodules suggesting a direct role of these markers in the onset, progression and recurrence of the disease. Our observations suggest that TGF-β1, IL-1β and VEGFa may be considered potential therapeutic targets in the treatment of Dupuytren’s disease. Moreover, a new innovative therapy may be represented by the combined use of specific inhibitors of these growth factors

Oxidative stress and inflammation biomarker expression in obstructive sleep apnea patients

Obstructive Sleep Apnea Syndrome (OSAS) is a respiratory sleep disorder characterised by repeated episodes of partial or complete obstruction of the upper airway during the night. This obstruction usually occurs with a reduction (hypopnea) or complete cessation (apnea) of the airflow in the upper airways with the persistence of thoracic-diaphragmatic respiratory movements. During the hypopnea/apnea events, poor alveolar ventilation reduces the oxygen saturation in the arterial blood (SaO2) and a gradual increase in the partial arterial pressure of carbon dioxide (PaCO2). The direct consequence of the intermittent hypoxia is an oxidative imbalance, with reactive oxygen species production and the inflammatory cascade's activation with pro and anti-inflammatory cytokines growth. Tumour necrosis factors, inflammatory cytokines (IL2, IL4, IL6), lipid peroxidation, and cell-free DNA have been found to increase in OSAS patients. However, even though different risk-related markers have been described and analysed in the literature, it has not yet been clarified whether specified inflammatory bio-markers better correlates with OSAS diagnosis and its clinical evolution/comorbidities. We perform a scientific literature review to discuss inflammatory and oxidative stress biomarkers currently tested in OSAS patients and their correlation with the disease's severity and treatment